crossing96/oncoscreening huggingface dataset:
Immunological Hallmarks for Clinical Response to BCG in Bladder Cancer.	Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumor activity. We observed the temporal changes of peripheral immune subsets including NKT cells, central memory CD4(+) T cells, CD8(+) T cells and regulatory T cells (Treg) during the course of BCG. Gene expression analysis revealed enriched immune pathways involving in T cell activation and chemotaxis, as well as a more diversified T cell receptor repertoire in post-BCG tissues. Moreover, tissue multiplexed-immunofluorescence (mIF) showed baseline densities of non-Treg and CD8(+)PD-1(+) T cells were predictive of response and better recurrence-free survival after BCG. Remarkably, post-BCG tissues from responders were found to be infiltrated with more active CD8(+)PD-1(-) T cells and non-Treg CD4(+)FOXP3(-) T cells; but increased exhausted CD8(+)PD-1(+) T cells were found in non-responders. Taken together, we identified predictive biomarkers for response and uncovered the post-treatment expansion of exhausted PD-1(+)CD8(+) T cells as key to BCG resistance, which could potentially be restored by combining with anti-PD-1 immunotherapy.	bladder
Staging (18)F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Changes Treatment Recommendation in Invasive Bladder Cancer.	Given the high risk of systemic relapse following initial therapy for muscle-invasive bladder cancer (MIBC), improved pretreatment staging is needed. We evaluated the incremental value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) after standard conventional staging, in the largest cohort of MIBC patients to date. This is a retrospective analysis of 711 consecutive patients with invasive urothelial bladder cancer who underwent staging contrast-enhanced CT (chest and abdomen) and FDG-PET/CT in a tertiary referral center between 2011 and 2020. We recorded the clinical stage before and after FDG-PET/CT and treatment recommendation based on the stage before and after FDG-PET/CT. Clinical stage changed after FDG-PET/CT in 184/711 (26%) patients. Consequently, the recommended treatment strategy based on imaging changed in 127/711 (18%) patients. In 65/711 (9.1%) patients, potential curative treatment changed to palliative treatment because of the detection of distant metastases by FDG-PET/CT. Fifty (7.0%) patients were selected for neoadjuvant/induction chemotherapy based on FDG-PET/CT. Moreover, FDG-PET/CT detected lesions suspicious for second primary tumors in 15%; a second primary malignancy was confirmed in 28/711 (3.9%), leading to treatment change in ten (1.4%) patients. Contrarily 57/711 (8.1%) had false positive secondary findings. In conclusion, FDG-PET/CT provides important incremental staging information, which potentially influences clinical management in 18% of MIBC patients, but leads to false positive results as well. PATIENT SUMMARY: In this report, we investigated the impact of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scanning on treatment of bladder cancer patients. We found that FDG-PET/CT potentially influences the treatment of almost one-fifth of patients. We therefore suggest performing FDG-PET/CT as part of bladder cancer staging.	bladder
Quality of Life After Bladder Cancer: A Cross-sectional Survey of Patient-reported Outcomes.	BACKGROUND: Little is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC). OBJECTIVE: To determine this, we undertook a cross-sectional survey covering 10% of the English population. DESIGN, SETTING, AND PARTICIPANTS: Participants 1-10 yr from diagnosis were identified through national cancer registration data. INTERVENTION: A postal survey was administered containing generic HRQOL and BC-specific outcome measures. Findings were compared with those of the general population and other pelvic cancer patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generic HRQOL was measured using five-level EQ-5D (EQ-5D-5L) and European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. BC-specific outcomes were derived from EORTC QLQ-BLM30 and EORTC QLQ-NMIBC24. RESULTS AND LIMITATIONS: A total of 1796 surveys were completed (response rate 55%), including 868 (48%) patients with non-muscle-invasive BC, 893 (50%) patients who received radiotherapy or radical cystectomy, and 35 (1.9%) patients for whom treatment was unknown. Most (69%) of the participants reported at least one problem in any EQ-5D dimension. Age/sex-adjusted generic HRQOL outcomes were similar across all stages and treatment groups, whilst problems increased with age (problems in one or more EQ-5D dimensions: <65 yr [67% {95% confidence interval or CI: 61-74}] vs 85+ yr [84% {95% CI: 81-89}], p =  0.016) and long-term conditions (no conditions [53% {95% CI: 48-58}] vs more than four conditions [94% {95% CI: 90-97}], p < 0.001). Sexual problems were reported commonly in men, increasing with younger age and radical treatment. Younger participants (under 65 yr) reported more financial difficulties (mean score 20 [95% CI: 16-25]) than those aged 85+ yr (6.8 [4.5-9.2], p <  0.001). HRQOL for BC patients (for comparison, males with problems in one or more EQ-5D dimensions 69% [95% CI: 66-72]) was significantly worse than what has been found after colorectal and prostate cancers and in the general population (51% [95% CI: 48-53], all p <  0.05). CONCLUSIONS: HRQOL following BC appears to be relatively independent of disease stage, treatment, and multimodal care. Issues are reported with sexual function and financial toxicity. HRQOL after BC is worse than that after other pelvic cancers. PATIENT SUMMARY: Patients living with bladder cancer often have reduced quality of life, which may be worse than that for other common pelvic cancer patients. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.	bladder
The impact of carcinoma in situ in ureteral margins during radical cystectomy: A case-controlled study.	BACKGROUND AND OBJECTIVE: The presence of carcinoma in situ (Cis) in association with bladder cancer is associated with a poor prognosis. However, the prognosis associated with the presence of Cis in ureteral margins (CUM) during radical cystectomy has been poorly defined. To assess the prognosis associated with the presence of Cis in ureteral margins in patients with pM0 bladder cancer who have not undergone neoadjuvant chemotherapy. MATERIALS AND METHODS: A retrospective case-control study was conducted between 2001 and 2016 using data from one academic center in France. From 1,450 radical cystectomies, 122 patients (case) who had CUM were matched according to age, sex, pTNM stage and urinary diversion method with a population sample of 122 patients (controls) who did not have Cis in ureteral margins during radical cystectomy. The survival analysis was performed by Kaplan-Meier using a (95%) CI. Multivariate Cox regression analysis was used to test the effect of CUM on cancer-specific survival. Recurrence-free survival was defined as a recurrence of urothelial carcinoma in the upper urinary tract. RESULTS AND LIMITATIONS: The mean follow-up period was 55.43 ± 39.6 months. The rate of Cis in the bladder in the CUM cases group was evaluated at 11.47%. The median overall and specific survival was inferior in the CUM cases group estimated at 43.3 [35.33-56.93] months, 52.43 [42.16-68.93] months respectively compared to the control group with a significant difference (P= 0.001, P= 0.0039). The cumulative probability of urothelial recurrence-free survival was decreased in the case group compared with the control group (63.9% vs. 92.6%, P = 0.0001). Multivariate analysis shown that urothelial recurrence was associated with CUM [(P <0.001), (HR adjusted =11.31), (95% CI): (3.38-37.77)] and the macroscopic appearance of the ureter (thickened, dilated) [(P= 0.003), (HR adjusted =4.62), (95% CI): (3.31-8.84)]. CONCLUSION: CUM is a poor prognostic factor that impacts cancer-specific survival and Recurrence-free survival. The presence of CUM has been independently associated with a significant increase in the risk of urothelial recurrence, and a decrease in both overall and specific survival. This supports the use of frozen section analysis to complete radical cystectomy without CUM.	bladder
Developing Tumor Radiosensitivity Signatures Using LncRNAs.	Long non-coding RNAs (lncRNAs) are involved in diverse biological processes, including DNA damage repair, and are of interest as potential biomarkers of radiosensitivity. We investigated whether lncRNA radiosensitivity signatures could be derived for use in cancer patients treated with radiotherapy. Signature development involved radiosensitivity measurements for cell lines and primary tumor samples, and patient outcome after radiotherapy. A 10-lncRNA signature trained on radiosensitivity measurements in bladder cell lines showed a trend towards independent validation. In multivariable analyses, patients with tumors classified as radioresistant by the lncRNA signature had poorer local relapse-free survival (P = 0.065) in 151 patients with muscle-invasive bladder cancer who underwent radiotherapy. An mRNA-based radiosensitivity index signature performed similarly to the lncRNA bladder signature for local relapse-free survival (P = 0.055). Pathway analysis showed the lncRNA signature associated with molecular processes involved in radiation responses. Knockdown of one of the lncRNAs in the signature showed a modest increase in radiosensitivity in one cell line. An alternative approach involved training on primary cervical tumor radiosensitivity or local control after radiotherapy. Both approaches failed to generate a cervix lncRNA radiosensitivity signature, which was attributed to the age of samples in our cohorts. Our work highlights challenges in validating lncRNA signatures as biomarkers in archival tissue from radiotherapy cohorts, but supports continued investigation of lncRNAs for a role in radiosensitivity.	bladder
Eosinophilic cystitis mimicking bladder cancer-considerations on the management based upon a case report and a review of the literature.	The hypereosinophilic syndrome (HES) is a rare disorder characterized by hypereosinophilia and infiltration of various organs with eosinophils. Eosinophilic cystitis (EC), mimicking bladder cancer clinically but also in ultrasound and in radiographic imaging, is one potential manifestation of the HES occurring in adults as well as in children. This case report describes the course of disease in a 57-year-old male presenting with severe gait disorders and symptoms of a low compliance bladder caused by a large retropubic tumor. After extensive urine and serologic examination and histologic confirmation of EC the patient was subjected to medical treatment with cetirizine and prednisolone for 5 weeks. While gait disorders rapidly resolved, micturition normalized only 10 months after initiation of therapy. Based upon this course the authors recommend patience and reluctance concerning radical surgical intervention in EC. Key Points • Eosinophilic cystitis is a rare condition with app. 200 cases reported, so far. • Etiology of eosinophilic cystitis is obscure, but allergies and parasitic infections may trigger the disease. • Genetic alterations (e.g., BRAF mutations) may predispose for the disease • Corticosteroids and antihistamines are the backbone of therapy and may be complemented by antibiotics and non-steroidal anti-inflammatory drugs in case of concomitant (underlying) infections. • As recovery can occur even after a long time, radical surgery should be restricted to highly selected cases.	bladder
ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma.	BACKGROUND: Bladder carcinoma is one of the most common urological cancers. ITPR3, as a ubiquitous endoplasmic reticulum calcium channel protein, was reported to be involved in the development and progression of various types of cancer. However, the potential roles and molecular mechanism of ITPR3 in bladder cancer are still unclear. Herein, we elucidated a novel role of ITPR3 in regulating the proliferation, metastasis, and stemness of bladder cancer cells. METHODS: The expression of ITPR3 in bladder cancer was analyzed using public databases and bladder cancer tissue microarrays. To demonstrate the role of ITPR3 in regulating the NF-ĸB/CD44 pathway and the progression of bladder cancer, a series of molecular biology and biochemistry methods was performed on clinical tissues, along with in vivo and in vitro experiments. The methods used included western blot assay, quantitative RT-PCR assay, immunofluorescence assay, immunohistochemistry (IHC) assays, wound healing assay, Transwell assay, colony formation assay, tumorsphere formation assay, cell flow cytometry analysis, EdU assay, MTT assay, cell transfection, bisulfite sequencing PCR (BSP), a xenograft tumor model and a tail vein cancer metastasis model. RESULTS: Higher ITPR3 expression was found in bladder cancer tissues and bladder cancer cells compared with the corresponding normal peritumor tissues and SV-HUC-1 cells, which was attributed to demethylation in the ITPR3 promoter region. ITPR3 promoted the proliferation of bladder cancer by accelerating cell cycle transformation and promoted local invasion and distant metastasis by inducing epithelial-to-mesenchymal transition (EMT). Meanwhile, ITPR3 maintained the cancer stemness phenotype by regulating CD44 expression. NF-κB, which is upstream of CD44, also played a critical role in this process. CONCLUSIONS: Our study clarifies that ITPR3 serves as an oncogene in bladder cancer cells and represents a novel candidate for bladder cancer diagnosis and treatment.	bladder
circST6GALNAC6 suppresses bladder cancer metastasis by sponging miR-200a-3p to modulate the STMN1/EMT axis.	Bladder cancer (BCa) is an aggressive malignancy because of its distant metastasis and high recurrence rate. Circular RNAs (circRNAs) exert critical regulatory functions in cancer progression. However, the expression patterns and roles of circRNAs in BCa have not been well investigated. In this study, we first screened circRNA expression profiles using a circRNA microarray of paired BCa and normal tissues, and the expression of circST6GALNAC6 was confirmed by qRT-PCR and fluorescence in situ hybridization (FISH). MTT, colony formation and Transwell assays were performed to measure cell proliferation, migration and invasion. We investigated the regulatory effect of circST6GALNAC6 on miRNA and its target genes to explore the potential regulatory mechanisms of circST6GALNAC6 by chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), MS2-tagged RNA affinity purification (MS2-TRAP), immunofluorescence (IF) and dual luciferase activity assays. A nude mouse xenograft model was used to examine the functions of circST6GALNAC6/STMN1 in tumour metastasis in vivo. We found that 881 circRNAs were significantly dysregulated in BCa tissues compared to normal tissues. circST6GALNAC6(hsa_circ_0088708) was downregulated in BCa tissues and cells. Overexpression of circST6GALNAC6 effectively inhibited the cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and suppressed BCa metastasis in vivo. Mechanistically, we showed that the SP1 transcription factor, which binds to the circST6GALNAC6 mRNA transcript, activates circST6GALNAC6 transcription. Next, we verified that circST6GALNAC6 serves as a sponge that directly binds miR-200a-3p to regulate stathmin (STMN1) expression. Furthermore, we found that STMN1 is involved in circST6GALNAC6/miR-200a-3p axis-regulated BCa EMT and metastasis. Thus, our findings indicate an important underlying mechanism in BCa metastasis by which SP1-induced circST6GALNAC6 sponges miR-200a-3p to promote STMN1/EMT signalling. This mechanism could provide pivotal potential prognostic biomarkers and therapeutic targets for BCa.	bladder
TERT Promoter Mutation Analysis of Whole-Organ Mapping Bladder Cancers.	BACKGROUND: Multifocal occurrence is a main characteristic of urothelial bladder cancer (UBC). Whether urothelial transformation is caused by monoclonal events within the urothelium, or by polyclonal unrelated events resulting in several tumor clones is still under debate. TERT promoter mutations are the most common somatic alteration identified in UBC. In this study, we analyzed different histological tissues from whole-organ mapping bladder cancer specimens to reveal TERT mutational status, as well as to discern how tumors develop. METHODS: Up to 23 tissues from nine whole-organ mapping bladder tumor specimens, were tested for TERT promoter mutations including tumor associated normal urothelium, non-invasive urothelial lesions (hyperplasia, dysplasia, metaplasia), carcinoma in situ (CIS) and different areas of muscle invasive bladder cancers (MIBC). The mutational DNA hotspot region within the TERT promoter was analyzed by SNaPshot analysis including three hot spot regions (-57, -124 or -146). Telomere length was measured by the Relative Human Telomere Length Quantification qPCR Assay Kit. RESULTS: TERT promoter mutations were identified in tumor associated normal urothelium as well as non-invasive urothelial lesions, CIS and MIBC. Analysis of separate regions of the MIBC showed 100% concordance of TERT promoter mutations within a respective whole-organ bladder specimen. Polyclonal events were observed in five out of nine whole-organ mapping bladder cancers housing tumor associated normal urothelium, non-invasive urothelial lesions and CIS where different TERT promoter mutations were found compared to MIBC. The remaining four whole-organ mapping bladders were monoclonal for TERT mutations. No significant differences of telomere length were observed. CONCLUSIONS: Examining multiple whole-organ mapping bladders we conclude that TERT promoter mutations may be an early step in bladder cancer carcinogenesis as supported by TERT mutations detected in tumor associated normal urothelium as well as non-invasive urothelial lesions. Since mutated TERT promoter regions within non-invasive urothelial lesions are not sufficient alone for the establishment of cancerous growth, this points to the contribution of other gene mutations as a requirement for tumor development.	bladder
Correlations between glycolysis with clinical traits and immune function in bladder urothelial carcinoma.	BACKGROUND: Glycolysis was a representative hallmark in the tumor microenvironment (TME), and we aimed to explore the correlations between glycolysis with immune activity and clinical traits in bladder urothelial carcinoma (BLCA). METHODS: Our study obtained glycolysis scores for each BLCA samples from TCGA by a single-sample gene set enrichment analysis (ssGSEA) algorithm, based on a glycolytic gene set. The relationship between glycolysis with prognosis, clinical characteristics, and immune function were investigated subsequently. RESULTS: We found that enhanced glycolysis was associated with poor prognosis and metastasis in BLCA. Moreover, glycolysis had a close correlation with immune function, and enhanced glycolysis increased immune activities. In other words, glycolysis had a positive correlation with immune activities. Immune checkpoints such as IDO1, CD274, were up-regulated in high-glycolysis group as well. CONCLUSION: We speculated that in BLCA, elevated glycolysis enhanced immune function, which caused tumor cells to overexpress immune checkpoints to evade immune surveillance. Inhibition of glycolysis might be a promising assistant for immunotherapy in bladder cancer.	bladder
The Evolving Landscape of Antibody-Drug Conjugates for Urothelial Carcinoma.	Metastatic urothelial carcinoma (UC) carries a poor prognosis and a 5-year overall survival of less than 5%, despite standard of care therapy using cisplatin-based chemotherapy and immune checkpoint inhibitors. Thus, novel agents that improve survival and have an acceptable toxicity profile are urgently needed. Antibody-drug conjugates (ADCs) represent a promising new treatment option that utilizes the targeting ability of an antibody to deliver cytotoxic drugs directly to tumors. Many ADCs are currently being investigated for treatment of UC, with enfortumab vedotin being recently approved by the US Food and Drug Administration for treatment of metastatic UC with progressive disease after chemotherapy and/or immune checkpoint inhibitors. Overall, ADCs hold promise as a long-awaited treatment option for UC.	bladder
Progressive perioperative benefits of laparoscopy in combination with an ERAS (Enhanced Recovery After Surgery) protocol in radical cystectomy with ileal conduit.	INTRODUCTION: Although in the recent years, laparoscopy and Enhanced Recovery After Surgery (ERAS) protocols have improved postoperative recovery in radical cystectomy (RC), the clinical efficacy of their association remains unclear. Our objective is to analyze the possible benefits obtained from laparoscopic RC (LRC) and its subsequent combination with an ERAS (ERAS-LRC) protocol compared to open RC (ORC). MATERIAL AND METHODS: We analyzed 187 consecutive RCs with ileal conduit performed in our center, of which 139 met the inclusion criteria: 47 ORC, 39 LRC (both with conventional protocol) and 52 ERAS-LRCs. RESULTS: No significant differences were found regarding age, sex, BMI and ASA score between groups. ERAS-LRC obtained a shorter length of stay than LRC and ORC (median 8 [7-10]) vs. 13 [10-17] vs. 15 [13-19.5] days, respectively; P<.001). ERAS-LRC had a shorter stay in the ICU and less days of nasogastric tube (P<.001). Postoperative complications and readmission rates were similar among groups. Multivariate logistic regression showed that absence of complications, younger age and ERAS behaved as independent factors for shorter hospital stay, while ERAS was the only independent factor of lower readmission rate at 90 days. CONCLUSIONS: Although LRC presented perioperative benefits compared to ORC, the results were better after the implementation of an ERAS protocol. ERAS protocol had stronger impact on recovery than the surgical approach of the procedure.	bladder
Conservative management of primary malignant melanoma of the bladder: a case report.	BACKGROUND: Primary malignant melanoma (PMM) of the bladder represents a very rare clinic-pathologic entity. Given the rarity of the disease, the best treatment option is not well recognized. CASE PRESENTATION: We describe a case of neoplasm of the bladder in a 74 years-old Caucasian man presenting with massive hematuria. Based on clinical, instrumental and histological findings a diagnosis of PMM was made. The patient underwent trans urethral resection of bladder tumor plus intravesical Bacillus Calmette-Guérin. CONCLUSIONS: To make a correct diagnosis, clinical history, endoscopic evaluation, histopathological examination and immunohistochemistry, are necessary. Multidisciplinary evaluation is required to discriminate primary from metastatic malignant melanoma.	bladder